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Current Molecular Pharmacology


ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Letter Article

Chronic Royal Jelly Administration Induced Antidepressant-Like Effects Through Increased Sirtuin1 and Oxidative Phosphorylation Protein Expression in the Amygdala of Mice

Author(s): Thanh Trung Nguyen, Yuki Kambe* and Atsuro Miyata

Volume 14, Issue 2, 2021

Published on: 24 April, 2020

Page: [115 - 122] Pages: 8

DOI: 10.2174/1874467213666200424160153

Price: $65


Background: Major depressive disorder (MDD) is a common psychological disorder worldwide. However, one-third of patients with MDD are resistant to the present anti-depressant medicine, which regulates monoamine contents in the brain. Thus, another drug target is strongly required. Much evidence strongly suggests that sirtuin1, which is the key factor in regulating the mitochondrial activity, may be implicated in MDD.

Objective: Since it is suggested that royal jelly (RJ) ameliorated depressive-like behavior and affected mitochondrial activity in mice, we hypothesized that RJ could be an alternative medicine against MDD, which acts via sirtuin1 signaling to improve mitochondrial activity.

Methods: In the present study, we applied a mouse model of MDD to investigate the effect of RJ on the depressive-like behavior and the sirtuin1 signaling on mitochondrial activity.

Results: Our results indicated that either the oral administration of RJ for 12 days or single intracerebroventricular (i.c.v.) injection decreased the duration of immobility in the tail suspension test, which suggested that RJ had an antidepressant-like effect. Moreover, sirtuin1 protein expression increased in mice following RJ treatment in the amygdala region, but not in the other brain regions. Similarly, the expressions of oxidative phosphorylation (OXPHOS) related proteins increased in the amygdala regions, but not in the hippocampal regions.

Conclusion: The increase of sirtuin1 and OXPHOS protein expression may at least in part contribute to the antidepressant-like effect of the RJ pathway, and RJ may have the potential to be a novel anti-depressant drug.

Keywords: Royal jelly, tail suspension test, major depressive disease, sirtuin1, oxidative phosphorylation, mitochondria.

Graphical Abstract
Manji, H.; Kato, T.; Di Prospero, N. A.; Ness, S.; Beal, M. F.; Krams, M.; Chen, G. Impaired mitochondrial function in psychiatric disorders. Nature reviews , 2012, 13(5), 293-307.
Kambe, Y.; Miyata, A. Potential Involvement of Mitochondrial Dysfunction in Major Depressive Disorder: Recent Evidence. Arch Depress Anxiety, 2015, 1(1), 019-028.
Kambe, Y.; Miyata, A. Potential involvement of the mitochondrial unfolded protein response in depressive-like symptoms in mice. Neurosci. Lett., 2015, 588, 166-171.
[] [PMID: 25576703]
Kasahara, T.; Kubota, M.; Miyauchi, T.; Noda, Y.; Mouri, A.; Nabeshima, T.; Kato, T. Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes. Mol. Psychiatry, 2006, 11(6), 577-93, 523.
Kasahara, T.; Takata, A.; Kato, T.M.; Kubota-Sakashita, M.; Sawada, T.; Kakita, A.; Mizukami, H.; Kaneda, D.; Ozawa, K.; Kato, T. Depression-like episodes in mice harboring mtDNA deletions in paraventricular thalamus. Mol. Psychiatry, 2016, 21(1), 39-48.
[] [PMID: 26481320]
Beasley, C.L.; Pennington, K.; Behan, A.; Wait, R.; Dunn, M.J.; Cotter, D. Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: Evidence for disease-associated changes. Proteomics, 2006, 6(11), 3414-3425.
[] [PMID: 16637010]
Shao, L.; Martin, M.V.; Watson, S.J.; Schatzberg, A.; Akil, H.; Myers, R.M.; Jones, E.G.; Bunney, W.E.; Vawter, M.P. Mitochondrial involvement in psychiatric disorders. Ann. Med., 2008, 40(4), 281-295.
[] [PMID: 18428021]
Andreazza, A.C.; Shao, L.; Wang, J.F.; Young, L.T. Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder. Arch. Gen. Psychiatry, 2010, 67(4), 360-368.
[] [PMID: 20368511]
Cai, N.; Chang, S.; Li, Y.; Li, Q.; Hu, J.; Liang, J.; Song, L.; Kretzschmar, W.; Gan, X.; Nicod, J.; Rivera, M.; Deng, H.; Du, B.; Li, K.; Sang, W.; Gao, J.; Gao, S.; Ha, B.; Ho, H.Y.; Hu, C.; Hu, J.; Hu, Z.; Huang, G.; Jiang, G.; Jiang, T.; Jin, W.; Li, G.; Li, K.; Li, Y.; Li, Y.; Li, Y.; Lin, Y.T.; Liu, L.; Liu, T.; Liu, Y.; Liu, Y.; Lu, Y.; Lv, L.; Meng, H.; Qian, P.; Sang, H.; Shen, J.; Shi, J.; Sun, J.; Tao, M.; Wang, G.; Wang, G.; Wang, J.; Wang, L.; Wang, X.; Wang, X.; Yang, H.; Yang, L.; Yin, Y.; Zhang, J.; Zhang, K.; Sun, N.; Zhang, W.; Zhang, X.; Zhang, Z.; Zhong, H.; Breen, G.; Wang, J.; Marchini, J.; Chen, Y.; Xu, Q.; Xu, X.; Mott, R.; Huang, G.J.; Kendler, K.; Flint, J. Molecular signatures of major depression. Curr. Biol., 2015, 25(9), 1146-1156.
[] [PMID: 25913401]
Abdallah, C.G.; Jiang, L.; De Feyter, H.M.; Fasula, M.; Krystal, J.H.; Rothman, D.L.; Mason, G.F.; Sanacora, G. Glutamate metabolism in major depressive disorder. Am. J. Psychiatry, 2014, 171(12), 1320-1327.
[] [PMID: 25073688]
Jou, S.H.; Chiu, N.Y.; Liu, C.S. Mitochondrial dysfunction and psychiatric disorders. Chang Gung Med. J., 2009, 32(4), 370-379.
[PMID: 19664343]
Inczedy-Farkas, G.; Remenyi, V.; Gal, A.; Varga, Z.; Balla, P.; Udvardy-Meszaros, A.; Bereznai, B.; Molnar, M.J. Psychiatric symptoms of patients with primary mitochondrial DNA disorders. Behav. Brain Funct., 2012, 8, 9.
[] [PMID: 22329956]
Gardner, A.; Boles, R.G. Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2011, 35(3), 730-743.
[] [PMID: 20691744]
Tang, B.L. Sirt1 and the Mitochondria. Mol. Cells, 2016, 39(2), 87-95.
[] [PMID: 26831453]
Kambe, Y.; Miyata, A. Possible roles of mitochondrial dysfunctions and SIRT1 in major depressive disorder. Nippon Yakurigaku Zasshi, 2017, 150(4), 204-206.
[] [PMID: 28966220]
CONVERGE consortium. Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature, 2015, 523(7562), 588-591.
[] [PMID: 26176920]
Abe, N.; Uchida, S.; Otsuki, K.; Hobara, T.; Yamagata, H.; Higuchi, F.; Shibata, T.; Watanabe, Y. Altered sirtuin deacetylase gene expression in patients with a mood disorder. J. Psychiatr. Res., 2011, 45(8), 1106-1112.
[] [PMID: 21349544]
Abe-Higuchi, N.; Uchida, S.; Yamagata, H.; Higuchi, F.; Hobara, T.; Hara, K.; Kobayashi, A.; Watanabe, Y. Hippocampal Sirtuin 1 Signaling Mediates Depression-like Behavior. Biol. Psychiatry, 2016, 80(11), 815-826.
[] [PMID: 27016384]
Menzies, K.; Auwerx, J. An acetylation rheostat for the control of muscle energy homeostasis. J. Mol. Endocrinol., 2013, 51(3), T101-T113.
[] [PMID: 23999889]
Delkhoshe-Kasmaie, F.; Malekinejad, H.; Khoramjouy, M.; Rezaei-Golmisheh, A.; Janbaze-Acyabar, H. Royal jelly protects from taxol-induced testicular damages via improvement of antioxidant status and up-regulation of E2f1. Syst Biol Reprod Med, 2014, 60(2), 80-88.
[] [PMID: 24377747]
Honda, Y.; Fujita, Y.; Maruyama, H.; Araki, Y.; Ichihara, K.; Sato, A.; Kojima, T.; Tanaka, M.; Nozawa, Y.; Ito, M.; Honda, S. Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans. PLoS One, 2011, 6(8), e23527.
[] [PMID: 21858156]
Suzuki, K.M.; Isohama, Y.; Maruyama, H.; Yamada, Y.; Narita, Y.; Ohta, S.; Araki, Y.; Miyata, T.; Mishima, S. Estrogenic activities of Fatty acids and a sterol isolated from royal jelly. Evid. Based Complement. Alternat. Med., 2008, 5(3), 295-302.
[] [PMID: 18830443]
Hattori, N.; Nomoto, H.; Fukumitsu, H.; Mishima, S.; Furukawa, S. Royal jelly-induced neurite outgrowth from rat pheochromocytoma PC12 cells requires integrin signal independent of activation of extracellular signal-regulated kinases. Biomed. Res., 2007, 28(3), 139-146.
[] [PMID: 17625346]
Minami, A.; Matsushita, H.; Ieno, D.; Matsuda, Y.; Horii, Y.; Ishii, A.; Takahashi, T.; Kanazawa, H.; Wakatsuki, A.; Suzuki, T. Improvement of neurological disorders in postmenopausal model rats by administration of royal jelly. Climacteric, 2016, 19(6), 568-573.
[] [PMID: 27736245]
Ito, S.; Nitta, Y.; Fukumitsu, H.; Soumiya, H.; Ikeno, K.; Nakamura, T.; Furukawa, S. Antidepressant-like activity of 10-hydroxy-trans-2-decenoic Acid, a unique unsaturated Fatty Acid of royal jelly, in stress-inducible depression-like mouse model. Evid. Based Complement. Alternat. Med., 2012, 2012, 139140.
[] [PMID: 21799699]
Takahashi, Y.; Hijikata, K.; Seike, K.; Nakano, S.; Banjo, M.; Sato, Y.; Takahashi, K.; Hatta, H. Effects of Royal Jelly Administration on Endurance Training-Induced Mitochondrial Adaptations in Skeletal Muscle. Nutrients, 2018, 10(11), E1735.
[] [PMID: 30424505]
Azab, K.S.; Bashandy, M.; Salem, M.; Ahmed, O.; Tawfik, Z.; Helal, H. Royal jelly modulates oxidative stress and tissue injury in gamma irradiated male Wister Albino rats. N. Am. J. Med. Sci., 2011, 3(6), 268-276.
[] [PMID: 22540097]
Can, A.; Dao, D.T.; Terrillion, C.E.; Piantadosi, S.C.; Bhat, S.; Gould, T.D. The tail suspension test. J. Vis. Exp., 2012, (59), e3769.
[PMID: 22315011]
Can, A.; Dao, D.T.; Arad, M.; Terrillion, C.E.; Piantadosi, S.C.; Gould, T.D. The mouse forced swim test. J. Vis. Exp., 2012, (59), e3638.
[PMID: 22314943]
Paxinos, G.; Franklin, K.B.J. The Mouse Brain in Stereotaxic Coordinates; Academic Press, 2001.
Miura, A.; Kambe, Y.; Inoue, K.; Tatsukawa, H.; Kurihara, T.; Griffin, M.; Kojima, S.; Miyata, A. Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation. J. Biol. Chem., 2013, 288(45), 32720-32730.
[] [PMID: 24045949]
Price, N.L.; Gomes, A.P.; Ling, A.J.; Duarte, F.V.; Martin-Montalvo, A.; North, B.J.; Agarwal, B.; Ye, L.; Ramadori, G.; Teodoro, J.S.; Hubbard, B.P.; Varela, A.T.; Davis, J.G.; Varamini, B.; Hafner, A.; Moaddel, R.; Rolo, A.P.; Coppari, R.; Palmeira, C.M.; de Cabo, R.; Baur, J.A.; Sinclair, D.A. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab., 2012, 15(5), 675-690.
[] [PMID: 22560220]
Samuels, B.A.; Leonardo, E.D.; Gadient, R.; Williams, A.; Zhou, J.; David, D.J.; Gardier, A.M.; Wong, E.H.; Hen, R. Modeling treatment-resistant depression. Neuropharmacology, 2011, 61(3), 408-413.
[] [PMID: 21356220]
Wohleb, E.S.; Gerhard, D.; Thomas, A.; Duman, R.S. Molecular and Cellular Mechanisms of Rapid-Acting Antidepressants Ketamine and Scopolamine. Curr. Neuropharmacol., 2017, 15(1), 11-20.
[] [PMID: 26955968]
Kishi, T.; Yoshimura, R.; Kitajima, T.; Okochi, T.; Okumura, T.; Tsunoka, T.; Yamanouchi, Y.; Kinoshita, Y.; Kawashima, K.; Fukuo, Y.; Naitoh, H.; Umene-Nakano, W.; Inada, T.; Nakamura, J.; Ozaki, N.; Iwata, N. SIRT1 gene is associated with major depressive disorder in the Japanese population. J. Affect. Disord., 2010, 126(1-2), 167-173.
[] [PMID: 20451257]
Asama, T.; Matsuzaki, H.; Fukushima, S.; Tatefuji, T.; Hashimoto, K.; Takeda, T. Royal Jelly Supplementation Improves Menopausal Symptoms Such as Backache, Low Back Pain, and Anxiety in Postmenopausal Japanese Women. Evid. Based Complement. Alternat. Med., 2018, 2018, 4868412.
[] [PMID: 29853955]
Kim, H.D.; Hesterman, J.; Call, T.; Magazu, S.; Keeley, E.; Armenta, K.; Kronman, H.; Neve, R.L.; Nestler, E.J.; Ferguson, D. SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens. J. Neurosci., 2016, 36(32), 8441-8452.
[] [PMID: 27511015]
Zhang, J.Y.; Liu, T.H.; He, Y.; Pan, H.Q.; Zhang, W.H.; Yin, X.P.; Tian, X.L.; Li, B.M.; Wang, X.D.; Holmes, A.; Yuan, T.F.; Pan, B.X. Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner. Biol. Psychiatry, 2019, 85(3), 189-201.
[] [PMID: 30060908]
Ferguson, D.; Koo, J.W.; Feng, J.; Heller, E.; Rabkin, J.; Heshmati, M.; Renthal, W.; Neve, R.; Liu, X.; Shao, N.; Sartorelli, V.; Shen, L.; Nestler, E.J. Essential role of SIRT1 signaling in the nucleus accumbens in cocaine and morphine action. J. Neurosci., 2013, 33(41), 16088-16098.
[] [PMID: 24107942]
Cao, J.; Joyner, L.; Mickens, J.A.; Leyrer, S.M.; Patisaul, H.B. Sex-specific Esr2 mRNA expression in the rat hypothalamus and amygdala is altered by neonatal bisphenol A exposure. Reproduction, 2014, 147(4), 537-554.
[] [PMID: 24352099]
Bogdanova, O.V.; Kanekar, S.; D’Anci, K.E.; Renshaw, P.F. Factors influencing behavior in the forced swim test. Physiol. Behav., 2013, 118, 227-239.
[] [PMID: 23685235]
Reardon, S. Depression researchers rethink popular mouse swim tests. Nature, 2019, 571(7766), 456-457.
[] [PMID: 31337906]

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